Estrogen Plus Progestin Therapy

Cardiovascular Disorders and Probable Dementia
Estrogen plus progestin therapy should not be used for the prevention of
cardiovascular disease or dementia [see WARNINGS AND PRECAUTIONS, and
Clinical Studies].

The WHI Memory Study (WHIMS) estrogen plus progestin
ancillary study of the WHI reported an increased risk of developing probable
dementia in postmenopausal women 65 years of age or older during 4 years of
treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to
placebo. It is unknown whether this finding applies to younger postmenopausal
women [see WARNINGS AND PRECAUTIONS, Use in Specific Populations, and Clinical Studies].

Breast Cancer

In the absence of comparable data, these risks should
be assumed to be similar for other doses of CE and MPA and other combinations
and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be
prescribed at the lowest effective doses and for the shortest duration
consistent with treatment goals and risks for the individual woman.

Estrogen-Alone Therapy

Endometrial Cancer

There is an increased risk of endometrial cancer in a
woman with a uterus who uses unopposed estrogens. Adding a progestin to
estrogen therapy has been shown to reduce the risk of endometrial hyperplasia,
which may be a precursor to endometrial cancer. Adequate diagnostic measures,
including directed or random endometrial sampling when indicated, should be
undertaken to rule out malignancy in postmenopausal women with undiagnosed
persistent or recurring abnormal genital bleeding [see WARNINGS AND
PRECAUTIONS].

Cardiovascular Disorders and Probable Dementia

Estrogen-alone therapy should not be used for the
prevention of cardiovascular disease or dementia [see WARNINGS AND
PRECAUTIONS, and Clinical Studies].

The WHI estrogen-alone substudy reported increased
risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during
7.1 years of treatment with daily oral CE (0.625 mg)-alone, relative to placebo
[see WARNINGS AND PRECAUTIONS, and Clinical Studies].

The WHIMS estrogen-alone ancillary study of the WHI
reported an increased risk of developing probable dementia in postmenopausal
women 65 years of age or older during 5.2 years of treatment with daily CE
(0.625 mg)-alone, relative to placebo. It is unknown whether this finding
applies to younger postmenopausal women [see WARNINGS AND PRECAUTIONS,
Use in Specific Populations, and Clinical Studies].

In the absence of comparable data, these risks should
be assumed to be similar for other doses of CE and other dosage forms of
estrogens.

Estrogens with or without progestins should be
prescribed at the lowest effective doses and for the shortest duration
consistent with treatment goals and risks for the individual woman.